Conventional drug discovery is a complex iterative process in which “bets” are placed on drug leads which are then structurally modified and tested to provide clinical candidates meeting regulatory requirements. Successful drug development depends critically on proper choice of targets. Because of early decisions in the overall strategy for drug lead development, conventional programs are committed to a limited series of molecules from which only structurally related final candidates are selected. Conventional drug activity screens, however, are unable to produce a sufficiently diverse set of small molecule options as potential targets to expand opportunities for success. Developing the full potential for intervention strategies, therefore, depends not only on screening vast numbers of compounds against validated targets, but also on exploiting the full panoply of mechanisms and loci available for attack on any specific target, in a focused way. Despite this, drug development strategies, e.g., those that employ affinity labeling, continue to center on endogenous ligand binding sites. Strategies for systematically capitalizing on possible intervention sites along the entire surface of a biological molecule, e.g., a protein, have not yet evolved.